PROJECT SUMMARY/ABSTRACT I am an Associate Professor of Medicine at the University of Pittsburgh and hold secondary appointments in Immunology and Clinical and Translational Research. I have established a research program in patient- oriented research (POR) in HIV-associated pulmonary disease with a focus on chronic obstructive pulmonary disease (COPD) and the role of the lung microbiome in COPD development and progression. I am committed to mentoring highly-qualified junior investigators in pulmonary, infectious diseases, and internal medicine in POR related to HIV lung disease and infections. I have been at the forefront of investigations of HIV- associated lung diseases in the current era of antiretroviral therapy (ART) and am well-positioned to mentor junior investigators in this field. The institutional resources, the University of Pittsburgh Clinical and Translational Science Institute (CTSI) and its associated clinical research training programs, and the strong departmental and divisional support and commitment to the mission of training junior investigators will ensure the successful development of a mentoring program in POR in HIV-related pulmonary disease. My career goals in POR are: 1) to acquire new training relevant to my current projects including laboratory work and data analysis in microbiome studies, 2) to continue to support my research infrastructure and studies via NIH funding, 3) to continue my collaborations with other multicenter HIV studies for both my work and that of my trainees. My career goals in mentoring are: 1) to acquire formal mentoring training via coursework, 2) to expand training from experienced mentors, 3) to assist my current trainees in transitioning from K to R funding, 4) to teach in the Institute of Clinical Research Education (ICRE) Training Program, and 5) to take on new trainees at the fellowship, residency, and student levels. Over the course of the K24 award, I will continue to mentor my three current trainees and mentor five new research fellows and five new medicine residents or students. The overall hypothesis of this proposal is that the fungal mycobiome is linked to abnormal lung function and inflammation in HIV+ individuals. This hypothesis will be tested by the following aims: Aim 1) To test the hypothesis that the fungal lung mycobiome in HIV+ individuals with COPD differs from that in HIV+ subjects without COPD and is related to COPD progression; Aim 2) To test the hypothesis that fungal communities in the lung are associated with alterations in the lung environment; Aim 3) To test the hypothesis that fungal translocation is associated with COPD severity and progression in HIV. This project will provide an ideal training environment for mentoring junior investigators in a novel field of POR. We will utilize the clinical, translational, and scientific resources of the Pittsburgh HIV Lung Research Center. This award will allow sufficient time to increase my mentoring expertise, to enhance my research skills, and to help me guide trainees in POR studies by ensuring adequate effort for mentoring and for assisting trainees in career development and obtaining independent funding.

PROJECT NARRATIVE Chronic obstructive pulmonary disease (COPD) is an important cause of respiratory impairment in HIV+ persons and will likely increase as the HIV+ population continues to age. We will investigate the roles of the fungal mycobiome in the lung and fungal translocation in HIV-associated COPD and elucidate the impact of chronic infections in perpetuating inflammation and pulmonary function decline. Successful completion of the proposal will define mechanistic pathways underlying pulmonary disease in HIV infection and test a novel hypothesis that will directly inform current and future treatment trials.